Galenic development and pharmacokinetic profile of indapamide sustained release 1.5mg

In accordance with international guidelines recommending the use of low dos es of antihypertensive agents, a new formulation of indapamide - indapamide sustained release (SR)- has been developed. Indapamide has been used world wide for many years as an immediate release (IR) formulation at a dose of 2 .5mg. The IR formulation leads to plasma peaks of indapamide immediately af ter administration of the tablet. These peaks are responsible for possible unfavourable electrolyte or metabolic effects relating to indapamide blood concentrations. The SR formulation, by eliminating plasma peaks, allows a s moothing of the pharmacokinetic profile of indapamide. This new galenic formulation is based on a hydrophilic matrix tablet compos ed of a cellulose derivative, methylhydroxypropylcellulose (MHPC), and a bi nder, polyvinylpyrrolidone (povidone). The originality of the matrix lies i n the percentages of MHPC and povidone, which permit a linear release in vi tro of indapamide. After optimisation, the chosen ratio of these 2 constitu ents allowed the release of more than 70% of the dosage over 16 hours in a very reproducible manner. The 2 tested formulations (SR and IR) have the sa me bioavailability; however, the main pharmacokinetic parameters of the new SR 1.5mg formulation, calculated after single and repeated administration, show a profile typical of an SR formulation, i.e. a lower maximum concentr ation (C-max), a longer time to C-max, and the same minimum concentration a s the IR formulation. This new SR formulation, which allows a reduction in the daily dose of inda pamide from 2.5 to 1.5mg, leads to an improvement in its efficacy/tolerabil ity ratio, thereby meeting the recommendations of the international guideli nes for the treatment of essential hypertension.